Summary
The cardiovascular effects of injection of 5-HT and the 5-HT1A receptor agonists, 8-OH-DPAT and flesinoxan, into the hypothalamus of anesthetized spontaneously hypertensive rats (SHR) was investigated. Injection of 5-HT (10 μg) into the anterior hypothalamic (AH) region increased blood pressure by 16 ± 2%, but did not change heart rate. Injection of 8-OH-DPAT (5 μg) into this area did not affect blood pressure or heart rate. Pressor responses (16 ± 3%) were also observed following 5-HT (10 μg) administration directly into the ventromedial hypothalamic (VMH) area. In contrast, however, injection of 8-OH-DPAT (1.25, 2.5 and 5μg) into the VMH caused dose-dependent reductions in both blood pressure and heart rate (22 ± 4 and 15 ± 3%, respectively at the highest dose). Surprisingly, injection of the 5-HT1A receptor agonist flesinoxan (10 μg) into the VMH did not affect blood pressure or heart rate. The results, therefore, suggest that 5-HT1A receptors are not involved in the cardiovascular effects elicited via the AH and VMH nuclei of the hypothalamus and that 8-OH-DPAT in the VMH seems to possess properties other than 5-HT1A receptor agonism.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Azmitia, E. C., and Segal, M. (1978). An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat. J. Comp. Neurol. 179: 641–668.
Born, A. H., Saxena, P. R., and Verdouw, P. D. (1988). Further characterization of the 5-HT,-like receptors in the carotid circulation of the pig. Br. J. Pharmacol. 94: 327.
Born, A. H., Verdouw, P. D., and Saxena, P. R. (1989a). Carotid haemodynamics in pigs during infusions of 8-OH-DPAT: reduction in arteriovenous shunting is mediated by 5-HT,-like receptors. Br. J. Pharmacol. 96: 125–132.
Born, A. H., Villalón, C. M., Verdouw, P. D., and Saxena, P. R. (1989b). The 5-HT,-like receptor mediating reduction of porcine carotid arteriovenous shunting by RU 24969 is not related to either the 5-HT,A or the 5-HT1e subtype. Eur. J. Pharmacol. 171: 87–96.
Connor, H. E., and Higgins, G. A. (1990). Cardiovascular effects of 5-HT,A receptor agonists injected into the dorsal raphe nucleus of conscious rats. Eur. J. Pharmacol. 182: 63–72.
Dreteler, G. H., Wouters, W., and Saxena, P. R. (1990). Comparison of the cardiovascular effects of flesinoxan with that of 8-OH-DPAT in the rat. Eur. J. Pharmacol. 180: 339–349.
Dreteler, G. H., Wouters, W., Saxena, P. R., and Ramage, A. G. (1991). Pressor effects following microinjection of 5-HTIA receptor agonists into the raphe obscurus of the anaesthetized rat. Br. J. Pharmacol. 102: 317–322.
Faiers, A. A., Calaresu, F. R., and Mogenson, G. J. (1976). Factors affecting cardiovascular responses to stimulation of hypothalamus in the rat. Exp. Neurol. 51: 188–206.
Fozard, J. R., Mir, A. K., and Middlemiss, D. N. (1987). Cardiovascular response to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat: site of action and pharmacological analysis. J. Cardiovasc. Pharmacol. 9: 328–347.
Gradin, K., Pettersson, A., Hedner, T., and Persson, B. (1985). Acute administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) a selective 5-HT receptor agonist, causes a biphasic blood pressure response and a bradycardia in the normotensive SpragueDawley rat and in the spontaneously hypertensive rat. J. Neur. Transm. 62: 305–319.
Kuhn, D. M., Wolf, W. A., and Lovenberg, W. (1980). Review of the role of the central serotonergic neuronal system in blood pressure regulation. Hypertension 2: 243–255.
Lambert, G., Friedman, E., and Gershon, S. (1975). Centrally mediated cardiovascular responses to 5-HT. Life Sci. 17: 915–920.
Lambert, G. A., Friedman, E., Buchweitz, E., and Gershon, S. (1978). Involvement of 5-hydroxytryptamine in the central control of respiration, blood pressure and heart rate in the anesthetized rat. Neuropharmacol. 17: 807–813.
Laubie, M., Drouillat, M., Dabire, H., Chergui, C., and Schmitt, H. (1988). Ventrolateral medullary pressor area: site of hypotensive and sympathoinhibitory effects of (±)-8-OHDPAT in anaesthetised dogs. Eur. J. Pharmacol. 160: 385–394.
Martin, G. E., and Lis, E. V. (1985). Hypotensive action of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in spontaneously hypertensive rats. Arch. Int. Pharmacodyn. 273: 251–261.
Moore, R. Y., Halaris, A. E., and Jones, B. E. (1978). Serotonin neurons of the midbrain raphe: ascending projections. J. Comp. Neurol. 180: 417–438.
Newberry, N. R. (1989). 5-HT,, receptors mediate a hyperpolarisation of rate ventromedial hypothalamic neurones in vitro. Br. J. Pharmacol. 98: 809.
Paxinos, G., and Watson, C. (1982). The rat brain in stereotaxic co-ordinates. Academic Press, Sydney, Australia.
Perren, M. J., Feniuk, W., and Humphrey, P. P. A. (1991). Vascular 5-HT,-like receptors which mediate contraction of the dog isolated vein and carotid arterial vasoconstriction in anaesthetised dogs are not of the 5-HTIA or 5-HT,p subtype. Br. J. Pharmacol. 102: 191–197.
Ramage, A. G., and Fozard, J. R. (1987). Evidence that the putative 5-HTIA receptor agonists, 8-OH-DPAT and ipsapirone, have a central hypotensive action that differs from that of clonidine in anaesthetised cats. Eur. J. Pharmacol. 138: 179–191.
Saavedra, J. M., Palkovits, M., Brownstein, M. J., and Axelrod, J. (1974). Serotonin distribution in the nuclei of the rat hypothalamus and preoptic region. Brain Res. 77: 157–165.
Saxena, P. R. and Villalón, C. M. (1990). Brain 5-HT,A receptor agonism: a novel mechanism for antihypertensive action. Trends Pharmacol. Sci. 11: 95–96.
Smits, J. F. M., Van Essen, H., and Struyker-Boudier, H. A. J. (1978). Serotonin mediated cardiovascular responses to electrical stimulation of the raphe nuclei in the rat. Life Sci. 23: 173–178.
Smits, J. F. and Struyker-Boudier, H. A. (1976). Intrahypothalamic serotonin and cardiovascular control in rats. Brain Res. 111: 422–427.
Valenta, B., and Singer, E. A. (1990). Hypotensive effects of 8-hydroxy-2-(di-n-propylamino)tetralin and 5-methylurapidil following stereotaxic microinjection into the ventral medulla of the rat. Br. J. Pharmacol. 99: 713–716.
Van Heuven-Nolsen, D., Tysse Klasen, T. H. M., Luo, Q., and Saxena, P. R. (1990). 5-HT,-like receptors mediate contractions in the rabbit saphenous vein. Eur. J. Pharmacol. 191: 375–382.
Vergé, D., Daval, G., Marcinkiewicz, M., Patey, A., El Mestikawy, S., Gozlan, H., and Hamon, M. (1986). Quantitative autoradiography of multiple 5-HT, receptor subtypes in the brain of control or 5, 7-dihydroxytryptamine-treated rats. J. Neurosci. 6: 3474–3482.
Wouters, W., Hartog, J., and Bevan, P. (1988a). Flesinoxan. Cardiovasc. Drug Rev. 6: 71–83.
Wouters, W., Tulp, M. T. M., and Bevan, P. (1988b). Flesinoxan lowers blood pressure and heart rate in cats via 5-HTIA receptors. Eur. J. Pharmacol. 149: 213–223.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Birkhäuser Verlag Basel/Switzerland
About this chapter
Cite this chapter
Dreteler, G.H., Wouters, W., Saxena, P.R. (1991). Cardiovascular Effects of Injection of 5-HT, 8-OH-DPAT and Flesinoxan into the Hypothalamus of the Rat. In: Fozard, J.R., Saxena, P.R. (eds) Serotonin: Molecular Biology, Receptors and Functional Effects. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7259-1_28
Download citation
DOI: https://doi.org/10.1007/978-3-0348-7259-1_28
Publisher Name: Birkhäuser Basel
Print ISBN: 978-3-0348-7261-4
Online ISBN: 978-3-0348-7259-1
eBook Packages: Springer Book Archive